Do you wonder which anti-aging ingredients really work? Today we’re reviewing the evidence for hyaluronic acid.

Which anti-aging ingredients really work?

When it comes to anti-aging products it’s easy to be tricked into spending a lot of money on products that aren’t worth it. That’s because there’s so much pseudoscientific misinformation out there about anti-aging cosmetic ingredients. Also, once you buy an anti-aging product, it takes you a long time to determine if it’s really working for you or not. That’s why we’re going to focus some of our podcast episodes on specific anti-aging ingredients, Today we’re talking about hyaluronic acid.

What is hyaluronic acid?

Think of it as a large sugar molecule, what chemists would call a polysaccharide. But it’s a BIG sugar. Regular table sugar has a molecular weight of about 340 units (Daltons). HA has a MW of anywhere from 600,000 to 1,000,000 units. Its structure and this large weight give it the ability to hold between 500 and 1000 times its own weight in water. That’s why our bodies use it to hydrate tissues and lubricate joints.

The many names of hyaluronic acid

First let’s talk about the name…This ingredient is most commonly referred to as hyaluronic acid which obviously is the acid form. Another version is the sodium salt which is officially known as sodium hyaluronate. These two terms are used interchangeably. The official INCI Name is Sodium hyaluronic acid. Just to make things more confusing, it’s sometimes referred to as “Hyaluronan” which is the generic name that covers all forms of HA. Finally there are 2 alternate versions which we’re aware of.

Sodium acetyl hyaluronate

Hydrolyzed hyaluronic acid

Where does hyaluronic acid come from?

The quick answer is it comes from animals. At least it’s found in mammals I’m not sure if it’s present in reptiles or fish. It might give you a little perspective if we went through a quick timeline starting from when hyaluronic acid was discovered.

1934 – Hyaluronic acid was first isolated from cow eyes in 1934 and it was given its name from the term “hyaloid” which means glassy. (Because hyaluronic acid gel is so clear and glass like.)

1930-40s – Hyaluronic acid was isolated from other sources including umbilical cords and rooster combs.

1951 – Chemists first determined the structure of hyaluronic acid.

1970s – We began to understand how hyaluronic acid interacts with cartilage which is why its such a good joint lubricant.

1980s- The 1980s saw the first cosmetic application of hyaluronic acid. When the stuff first burst on the antiaging scene I was working for a small high end cosmetics company that used it. At the time it was very expensive because it was sourced from rooster combs. As I recall it was about $500 a kilo maybe more.

1999- Researchers figured out how to clone hyaluronic acid from bacteria (specifically Group A Streptococcus). The bacterial type was lower molecular weight but it was cheaper and didn’t involve animal sourcing. But there’s some danger of contamination with strep toxins.

2003: The FDA approved hyaluronic acid approved as an injectable for facial lines and wrinkles.

2010 and beyond – In the last few years a new method has been developed that makes hyaluronic acid from a safe bacterial strain called Bacillus subtilis. So today state of the art hyaluronic acid is free from contamination, not made from animals, and is made without the use of organic solvents.

What does hyaluronic acid do?

We mentioned that hyaluronic acid is found in places like the fluid filled area of the eye and in joints. That’s because its ability to retain high levels of water. It’s also very viscous, very thick, yet it thins out during shear stress so hyaluronic acid is said to be “ideal as a biological lubricant.” The average person has about 15 grams of hyaluronic acid in their body at any given time and about one third of that is turned over every day. There are enzymes that produce hyaluronic acid and other enzymes that break it down so it’s constantly being recycled.

Restoring lost hyaluronic acid can be an effective treatment for a number of conditions. For example, it’s injected into joints to treat osteoarthritis. (It can be taken orally as well but it’s not as effective.) It’s also used in eye surgeries like cataract removal and cornea transplants where it is injected directly into the eye. And of course, it’s also found in skin, where it helps keep it plump and wrinkle free.

Over time our bodies produce less hyaluronic acid and that’s another contributing cause of wrinkles. And that brings us to the key question…is hyaluronic acid a good skin care ingredient? There are 3 or 4 different levels to that question because you can restore hyaluronic acid different ways. (Much like our discussion of collagen back in Episode 73)

It’s used as an injectable filler, a topical moisturizer, a cell communicating ingredient, and as a dietary supplement. Let’s look at each of these to see what hyaluronic acid really does for skin. Once again we’ll be using the three Kligman questions which as if science has a mechanism to explain HOW it works, if the ingredient PENETRATES skin, and if there are any credible studies proving that it works on real people. Let’s start by talking about hyaluronic acid as an injectable filler.

Hyaluronic acid as an injectable filler

It’s always easier to talk about a treatment that’s been approved by the FDA because you know there’s plenty of research behind it. In this case, we know that injectable hyaluronic acid really works to plump up wrinkles. The mechanism is simply the physical force of the high MW polymer. It penetrates because a needle is used to bypass the outer layers of skin, and we know it really works for for filling wrinkles and that it typically lasts for six months.

Of course, just as with collagen or any other filler, you have to visit a professional to have the treatment done, it can be rather expensive, HOW MUCH, and it has to be redone every several months. Even though it works this approach isn’t for everyone.

Hyaluronic acid as a moisturizer

Is there a mechanism?
The mechanism of moisturization is the way that hyaluronic acid can hold up to 1000 times its weight in water. It’s very unusual for a polymer to hold on to THAT much water.

Does it penetrate?
Since this kind of moisturization works at the surface of skin, hyaluronic acid doesn’t really need to penetrate in order to be able to work. It just has to be deposited on the surface of skin. That means it needs to be applied from a substantial, leave on product. Don’t waste your money on expensive hyaluronic acid products that are rinsed off (like cleansers) or ones that don’t apply a significant amount to your face (like a toner.)

Are there studies to prove it works?
Yes. For example, here’s one study from a 1999 Shiseido research paper that measured the moisturizing effect of hyaluronic acid the Sodium Acetyl version) on Guinea pig skin. It’s not difficult to prove this using a number of different techniques.

There is one interesting concern that has been raised about hyaluronic acid and other ingredients like glycerin that bind water to the skin: In dry climates, where there’s little moisture in the air, these ingredients may actually pull water OUT of the skin, and bring it to the surface where it can evaporate. In other words, these ingredients may actually make your skin drier. The best defense against that is to not rely on serums that are based ONLY on hyaluronic acid or glycerin. Instead, use a cream or lotion that also contains occlusive ingredients that can lock water into the skin.

So at the end of the day, hyaluronic acid is a good topical moisturizing ingredient but there are LOTS of good moisturizing ingredients out there. If you are going to spend a lot of money on an hyaluronic acid product at least make sure it contains a good level of hyaluronic acid. You’ll have to read the label carefully. Let’s look at a couple of examples:

Sephora sells Peter Thomas Roth’s “VIZ-1000™ 75 percent Hyaluronic Acid Complex.” When I saw this I thought wow, that’s a high concentration HA. I don’t even know if you can make it that concentrated. But when I looked at the ingredient list I saw a bunch of extracts listed first and hyaluronic acid was listed as the 25th or 26th ingredient. It was almost last. If this is truly a 75% hyaluronic acid product then it would have to be the first or second ingredient. What’s going on here? Read the name carefully – It’s the 75% hyaluronic acid COMPLEX. So what they’ve done is taken hyaluronic acid, mixed it with a bunch of extracts that don’t do anything, and used 75% of this mixture. That doesn’t mean it contains a useful level of hyaluronic acid! This may be a perfectly fine product but that’s a very shady way of approaching the marketing.

By comparison, look at this Skinceuticals Hydrating B5 Gel. It doesn’t even have hyaluronic acid in the name, yet its the second ingredient. Of course it could still be used at a low level but you have to appreciate the difference in marketing approach.

Hyaluronic acid as a “cell communicating” ingredient

Is there a mechanism?
Cell communicating ingredients are active ingredients that aren’t just superficial moisturizers. They may actually have an effect on underlying skin biology. I say “may” because the data on these ingredients is still sketchy and depending on the effect they have they could considered to be drugs. Still, there seems to be a growing body of evidence that some ingredients work this way. Surprisingly, hyaluronic acid may be in this category.

One study, performed at the University of Regensburg in Germany, measured the effect of hydrolyzed hyaluronic acid on gene expression. They used DNA-chip technology and reconstructed human skin to find that hydrolyzed hyaluronic acid changed the regulation of more than 40 genes including those responsible for cell to cell adhesion. Their conclusion was that this model could explain how hyaluronic acid improves skin tautness.

Another in vitro study found that supplemental hyaluronic acid may help stimulate collagen production. But this one was just done on cells in a lab and is not very definitive. Besides, hyaluronic acid is way too big to penetrate the skin. Right?

Does it penetrate?
I have to say that it was quite surprising for us to find out that hyaluronic acid may actually penetrate the skin! Why is this so surprising? Two reasons. First, hyaluronic acid molecules are too big. They’re about 3,000 nm in diameter and the space between skin cells is only about 15 to 50 nm. Theoretically there’s no way a molecule that large should be able to make its way through the skin. Second, hyaluronic acid is very hydrophilic, or water loving, and we know that to penetrate skin substances have to be more oleophillic, or oil loving. That’s why water soluble AHA’s are good on the surface of skin but oil soluble BHAs are better to penetrate pores to treat acne. So hyaluronic acid has two strikes against it.

But it turns out there are actually two ways hyaluronic acid may be penetrating. First, recent research in hydrolyzed hyaluronic acid shows that it can be made small enough to slip between these intercellular space. This hydrolyzed hyaluronic acid is chopped up into pieces with a molecular weight of about about 50 kDaltons. The researchers found that this could penetrate pigs ears. (Evonik study)

And second, the big shock was that even the full size molecules may be able to penetrate because the configuration of the molecule may over come the electric charge issue that comes from being hydrophilic. This was a 1999 study from the Journal of Investigative Dermatology titled Absorption of Hyaluronan Applied to the Surface of Intact Skin. The researchers radioactively tagged hyaluronic acid and applied it to both hairless mice and human forearm skin. Results showed that in both mice and humans, hyaluronic acid penetrated deep into the epidermis, the dermis and the lymphatic endothelium. They also found hyaluronic acid metabolites in blood and urine in the mice. This is the first and only study we’re aware of to show that full size hyaluronic acid penetrates deep into the dermis where it accumulates briefly before being degraded by enzymes. The researchers also said that not a lot ends up in the dermis and that it doesn’t stay there very long. But it really may penetrate!

Are there studies to prove it works?
The cell communicating properties of hyaluronic acid don’t seem to be very well studied yet but we did find a couple of relevant papers. One long term, placebo controlled in vivo study assessed the effect of hydrolyzed hyaluronic acid on skin elasticity and roughness. They found the formula with hyaluronic acid significantly increased elasticity (by about 14%) and significantly reduced roughness (by about 10%). That’s not a huge effect but it’s interesting.

Another study, from the The Journal of Clinical and Aesthetic Dermatology looked promising because it found that Hyaluronic acid can “boost skin’s moisture content, reduce inflammation, have cell-communicating abilities, and help prevent moisture loss.”

Finally, for what it’s worth, we found another study on “nano” hyaluronic acid which was reduced to 5nm so it could penetrate. But the study was NOT blind or placebo controlled. They just applied an HA cream for several weeks and the results are compared to untreated skin. http://jcadonline.epubxp.com/i/282497/17.

So, while we’d like to see more definitive research, it does appear that hyaluronic acid may be a cell communicating ingredient.

Hyaluronic acid as an ingestible dietary supplement

Is there a mechanism?
Finally let’s talk about hyaluronic acid as a dietary supplement. Mechanistically speaking this could work. We found a study titled “Dietary hyaluronic acid migrates into the skin of rats” which showed that when rats orally ingest radio-tagged hyaluronic acid, it shows up in their skin. About 90% of it was broken down in the digestive track but some did make its way to the dermis.

Does it penetrate?
Since it appears in blood and skin after ingestion, it appears to be “penetrating” via the digestive system.

Are there studies to prove it works?
Besides this study on rats we couldn’t find any studies on the benefits of ingested hyaluronic acid for skin in humans. The best thing we could find was a 2015 meta analysis of the studies using hyaluronic acid to treat osteoarthritis. According to the researchers, and I quote “Despite the American Academy of Orthopaedic Surgeons’ recommendation against the use of hyaluronic acid in OA, some systematic reviews found some benefits in the knee.” http://www.ncbi.nlm.nih.gov/pubmed/25633815. So that’s not very encouraging but the area is also not very well studied.

The Beauty Brains bottom line

Hyaluronic acid certainly works as an injectable but that’s not for everyone.

Hyaluronic acid is a good moisturizer but expensive compared to other options.

Hyaluronic acid MAY, repeat MAY have unexpected anti-aging properties but not fully understood.

There’s a mechanism to explain how it may benefit the skin when ingested but we couldn’t find any reliable studies confirming this on real people.

I am soooo grateful for this article! I read opposite opinions regarding the HA, but now I understand it much deeper, so thank you! 🙂 It is very nice that you can write so understandable even about chemistry topics.

That’s a great article especially pointing out the naughty marketing spin from PTR. I’ve ordered the CeraVe Moisturising Cream with HA which is apparently a great low cost option so look forward to trying that.
Randy, when you say people with dry skin should use it with with a serum that contains occlusive ingredients. Could you give an example of what those ingredients are? thanks

Great information. I do have a question. I was wondering if you could explain the difference between a low molecular weight HA and high molecular weight? I believe I read that low is best for skin. How can I tell which one I’m purchasing-if that’s even possible?

Hi Vicki: In terms of moisturization, higher MW is better because it can hold more water. However, lower MW MAY be better for skin penetration (which could mean better cell communicating.) Unfortunately, there’s no way to tell by looking at the label.

I am confused about the differences between sodium hyaluronate, hydrolyzed hyaluronic acid and cross linked? Do you think you could help me understand all these differences? What is the best? Thanks. I loved your article and wish I could share a link?

Sodium hyaluronate is just the salt form of hyaluronic acid. It’s really the same thing. Hydrolyzed hyaluronic acid is less effective at moisturizing because it’s broken into smaller bits. Cross linked, that’s the natural state of hyaluronic acid. It just refers to the internal bonds in the molecule.

An excellent article. Thanks so much for this post. Learn so much since I am a big fan of HA. I have been using it together with vitamin C, the result is fantastic. Would you provide more educational post in regards to vitamin C? Proline?

No, the FDA does not publish guidelines for cosmetic ingredients. “Good” is very subjective and but we just meant that it should be present at an efficacious level. Around 1% would be nice in a cream or lotion.

Thanks for the information. My mom is always talking about how much she wish she looked younger. It’s just that her skin is losing a lot of its elasticity. Anyway, this hyaluronic acid sounds like it could work really well for her. Like you said, it’s not for everyone, though. Do you have other product suggestions?

It’s great to see such a thorough scientific review of hyaluronic acid and how it acts on the skin. Of interest is in particular the information on HM/LM hyaluronic acid and which are likely to penetrate the skin, and also that hyaluronic acid is best applied with a good quality skin lotion to seal in the moisture.

Great article! Thank you so much for sharing this.. I have been looking at hyaluronic acid but thought that it’s “just” a humectant.. Now that I see there’s a probable anti-aging, cell-communicating side to it, it’s back in my must-have ingredients for a HG moisturizer.

Marta: We found the study on the website for Finecon, one of the suppliers of HA. I just checked the link and it doesn’t work anymore. I don’t know if they just changed the URL or if they’ve removed the study. If I find it, I’ll repost it.

Since hyaluronic acid holds moisture well–holding up to 1,000 times its weight in water–it functions not only to deliver water to the skin, but also to hold it there. As a large molecule, it does not permeate deep into the skin, but instead stays near the surface where it moisturizes the skin’s outer surface layers. I tried all the hyaluronic acid serums out there, but the most potent one for me is the Lady Soma Renewal Serum. It has a high concentration of hyaluronic acid, and doesn’t irritate my skin.

Thank you for taking the time to educate and write this interesting column on hyaluronic acid; I just started using bionect cream in the morning and on nights when I don’t apply atralin cream. The bionect seems to have a dry, somewhat tacky feel that makes it more difficult to apply even light makeup. What are your thoughts on applying a small amount of additional moisturizer with the bionect (i.e. Josie Maran Argon milk oil, neutragena, cerave, etc.) If acceptable would I moisturizer before or after bionect?
I also pat on Elta MD UV Clear (46spf) as a final step before light makeup.
Thanks much!

In my own skin care regimen, I’ve found hyaluronic acid to have positive effects when used as a face serum (My vitamin c serum used HA as a base). I find that these two ingredients tend to work quite effectively together.

I have been making a HA serum, however after a couple of days it loses its viscosity and becomes very watery. It does contain some Vitamin C as well. I would be very interested to know why that happens, and if the HA will still be effective.

Thanks for giving us the biological as opposed to economic sciences behind beauty trends.
It is nice to see research aggregated for us….so much easier than sussing out real vs. beauty industry studies. You guys know how to see who’s paying for flattering info on skin care. Something that most of us who don’t work in the industry, or advertising, have the time or inclination for.
Keep it up!

Dear Mr. Rabny,
This is really a great article, very informative and nicely explained.
It will be great if you can provide me guidance for below topics which i want to thorogh with:
1) How Hyaluronic acid act as cell communicating ingredient and ho that helps in anti aging treatment.
2)More detailed study on penetration of Hyaluronic acid in dermis layer of skin.

Hi Randy, Nice read, and very informative about Hyaluronic acid, and I am a big fan of HA to use it along with Vitamin C and E as a serum for a radiant, glowing, wrinkle free skin. Thanks for putting such a detailed post, and mentioning the use and benefits of HA even for healthier eyes and joints, and sharing some rally amazing facts like it could hold upto 1000 times its own weight under water .

High weight which sits closer to skin surface … Sort of a filler making lines/wrinkles less visible as well as improving surface hydration and look

The caveat with HA is, as you have noted, to be sure to use
topical humectants

Do I have above right? The bottom line supposedly is to use products containing multiple ..all three ..weights of hyaloronic acid

Your thoughts?

How does one determine weights ?
Should there be a variation in ratio?
Are there good moisturizers, serums, oils, products which have best combo?
What are best to consider…why?
Where can I find further info on above and choice…I definitely am dealing with TEWL …is there a recovery protocol you would suggest and other products to add but not overdo?

PS My skin is mature, now dry and flaky from a long autoimmune illness and too many Meds. I do have some rosacea. Few wrinkles but do have marionette/laugh lines …fair skin which looks younger, family trait…not as good since illness.

Looking better is part of my healing process BUT I am confused with so many products with big claims. I have gone back to Vaseline but am wary since so many negatives about petroleum. I do use vitamin C, a light liquid exfoliator at times, honey, avocado, toes hip oil and spray plus Cerave pm ..wondering about their moisturizer

Hi Mary Ann. You raise a lot of good question for which I don’t really have an answer, but let me try a few…

I’ve never heard of the low, medium and high HA approach that you outlined. It doesn’t really make sense based on what I know which is high MW is good for binding moisture, low is good for penetrating. The middle level sounds artificial to me.

The only way to determine which MW’s are used in a product is to contact the company and ask them pretty please to tell you.

Regarding vaseline – if you like the way it makes your skin feel, USE IT! The negatives you read about petrolatum are mostly fear mongering.

I’ve heard from some people that if you start to use anti-aging products like Hyaluronic acid at a young age (17 for example), and keep using these, that it will be detrimental for your skin in the long run because your skin will produce less of it sooner or something like that. Is this true?

“This makes no sense from a scientific perspective” Rude! This was a very Hillary (political) answer. How can you say this has no scientific perspective with out RESEARCH? This is tantamount to telling a person using steroids that it won’t affect your own body’s own growth hormone production when science tells us that it can. This can be very dangerous for drug users. How can we really say at this point if providing your body with an external source for moisturizing year after year will cause the body to down regulate its own natural moisturizing abilities.

I’m sorry if I came across as rude. I should have said that I’m not aware of any evidence that would support the mechanism that Melanie described in her question. I can’t say that it’s completely impossible (because it’s very hard to prove a negative) but I can say that the notion that using anti-aging products is “detrimental for your skin in the long run because your skin will produce less of it sooner or something like that” is inconsistent with the scientific consensus today.

I’m not sure what Hillary has to do with this or why you’re introducing your own political biases into a discussion on beauty science.

Teoxane, as far as I can tell from looking at their website, sells a line of dermal fillers that uses HA. These are not topical products, they are injectables that are delivered deep into your skin with a needle. Their marketing term for the type of HA they use is “resilient” but this is not a broadly used scientific description. (I’m guessing it has to do with how the HA is cross linked.)

Very informative website. Thank you.
I’ve been wanting to try HA serum but a lot of products are out there
and it’s so hard to pick one that really has the right amount of HA.
I will use what I learned from your advice in picking my HA serum.
You mentioned, it’s good to use it with moisturizer.
After applying, how many seconds, minutes should I apply the moisturizer.
Can I use No 7 product as my moisturizer.

Hyaluronic acid works for wrinkles because the molecule swells after it absorbs water, and that plumps lines on the spot. Look for products with hyaluronic acid listed near the top of the ingredient list, cause that means there is alot of it. I use Lady Soma’s Renewal Serum for my hyaluronic acid and will never stop using it. Its my favorite – and I am so happy everyone is into hyaluronic acid now because it does work!

Most informational web-sights on HA are simply not genuine. ALL the web sources that I have found speaking highly of the benefits of topical, and oral intake of HA are directly selling a product or use affiliate marketing to link you to companies that are. So most sights are out to make money. But lets be honest here. HA is simply to large to be absorbed by the epidermis layer and to large to be absorbed in the GI track. Don’t just ignore the language “it may be possible” or “this may suggest” or “this may penetrate”. This language only implies that it MIGHT work. There is no research that diffidently proves HA Taken orally of topically will improve knee function or make your skin look fuller and younger. But those of you that cant accept aging and the appearance of, just ignore what I said and waste your money.

Thanks for making this show about HA! I’ve been mixing my own HA from a recipe from Jane at Making Skincare. I love using my own formula and mixing it myself really brings the cost down. I live in a very dry climate though and now I am wondering if it is extracting water from my skin – I apply it morning and night. I am planning on making a new batch soon and am wondering what occlusive ingredients you would recommend to help the moisture stay locked into my skin? I tend to break out so I would love one that is non-comedogenic. So far allantoin seems like a good option. Thanks for your advice! –Heather

I am normal to oily skin, when apply the skinceuticals b5 gel alone. it makes skin taut and feel dehydrated. is that because the HA is evaporating since not sealed in? I thought I read HA works in low humidity too ??

Thanks for clearing a lot of concerns I had about HA. Even though I would prefer only natural and organic products (no animals used) in cosmetics, it is especially hard to find some good and effective skincare products with organic only ingredients. My experience with HA is good when it comes to moisturizing.

I am a regular user of Vitamin C serums that contain hyaluronic acid but not every time I look into the ingredients and decide on what is good or bad. But when it comes to face, things change. Your guide is amazing and helped me understand the pros and cons of HA.

Wow, that sounds really cool! However I’m rather suspicious when I hear about such anti-aging products because for me they all seem like only an advertisement, not the ones which can give the real effect. This substance seems interesting from what I read in your article but I didn’t understand about its effect, does it really help to stop the aging processes in case of body?
Besides I think that all such “magic” substances can be helpful only if you care about your body in general, I mean healthy diet, absence of bad habbits and regular physical exercises. I suppose that without this the effect will be too small.

My wife uses HA, I have noticed that it works very well for her wrinkles. I’m on the fence if I should use it as well. I know a lot of guys don’t talk about using anti-wrinkle creams but I figure it’s at least worth a try.

I’ve been using Hyaluronic Acid for a while. So far I am very pleased with the Lady Soma Renewal Serum (which contains hyaluronic acid) with it. No funky smell or stickiness. I have a combination skin type: dry and oily in t-zone area. My trick is to apply when my face is still wet when it feels really dry cause of the dry weather in California or apply right before.

Aw! Beautiful. The best of the best. Randy, could you give more info regarding an HA serum or cream. Do you know which product or brand is the best? As you mentioned in some product even the ingredients include 77% HA, but it’s not true. If I want to buy a serum or cream with the most % of AH, what do you recommend?

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